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Objective: Our objective was to investigate the mechanisms that govern natural killer (NK)-cell responses to HIV, with a focus on specific receptor--ligand interactions involved in HIV recognition by NK cells., Design and Methods: We first performed a mass cytometry-based screen of NK-cell receptor expression patterns in healthy controls and HIV individuals. We then focused mechanistic studies on the expression and function of T cell immunoreceptor with Ig and ITIM domains (TIGIT)., Results: The mass cytometry screen revealed that TIGIT is upregulated on NK cells of untreated HIV women, but not in antiretroviral-treated women. TIGIT is an inhibitory receptor that is thought to mark exhausted NK cells; however, blocking TIGIT did not improve anti-HIV NK-cell responses. In fact, the TIGIT ligands CD112 and CD155 were not upregulated on CD4 T cells in vitro or in vivo, providing an explanation for the lack of benefit from TIGIT blockade. TIGIT expression marked a unique subset of NK cells that express significantly higher levels of NK-cell-activating receptors (DNAM-1, NTB-A, 2B4, CD2) and exhibit a mature/adaptive phenotype (CD57, NKG2C, LILRB1, FcRγ, Syk). Furthermore, TIGIT NK cells had increased responses to mock-infected and HIV-infected autologous CD4 T cells, and to PMA/ionomycin, cytokine stimulation and the K562 cancer cell line., Conclusion: TIGIT expression is increased on NK cells from untreated HIV individuals. Although TIGIT does not participate directly to the response to HIV-infected cells, it marks a population of mature/adaptive NK cells with increased functional responses.

In Benin, consistent condom use among men who have sex with men (MSM) is relatively low and providing them with Pre-exposure prophylaxis (PrEP) could be of great relevance. We aimed to describe PrEP knowledge and intention to use it; identify key facilitators and barriers to PrEP; and describe the perceived impact of PrEP on unsafe sexual behavior. MSM, 18 years or older, HIV-negative or of unknown status, were enrolled in five cities of Benin. Intention to use PrEP was assessed through five focus groups (FG). Data were analyzed using manual thematic sorting. Thirty MSM (six per city) participated in the FG. Mean age (standard deviation) was 27.1 (5.0) years. All participants expressed the intention to use PrEP if made available. Facilitators of PrEP use were: availability of medication, safety, absence of constraints as well as freedom to have multiple sex partners and sex with HIV-positive friends. Barriers were: complex procedures for obtaining medication, size and taste of medication, cost of medication, poor PrEP awareness.. Eighteen men admitted that PrEP could lead to decrease in or even abandonment of condom use. In conclusion, MSM showed openness to use PrEP if available, although they recognized that it could lead to risk compensation. [ABSTRACT FROM AUTHOR]

Objectives: Female sex workers (FSWs) play a key role in HIV transmission in West Africa, while they have limited access to antiretroviral therapy (ART). In line with UNAIDS recommendations extending ART to all HIV-infected individuals, we conducted this demonstration project on immediate treatment as prevention (TasP) among FSWs in Cotonou, Benin. We report data on treatment response and its relation to adherence, as well as on ART-resistant genotypes. Methods: Complete follow-up varied between 12 and 24 months. At each three-monthly visit, a questionnaire was administered, clinical examinations were carried out and blood samples collected. Adherence to treatment was estimated by self-report. Viral RNA was genotyped at baseline and final visits for drug resistance. Generalized estimating equations for repeated measures with a log-binomial link were used to analyze time trends and the association between adherence and virological response to treatment. Results: One-hundred-seven HIV-positive and ART-naive FSWs were enrolled; 59.8% remained in the cohort till study completion and 62.6% had a final visit. Viral load<1000 (below quantification limit [<50]) was attained in 73.1% (64.6%) of participants at month-6, 84.8% (71.2%) at month-12, and 80.9% (65.1%) at the final visit. The proportion of women with suppressed (below quantification limit) viral load increased with increasing self-reported adherence (p = 0.06 (0.003), tests for trend). The proportion of participants with CD4≤500 also decreased drastically throughout follow-up (p <.0001). Twelve participants exhibited ART-resistant genotypes at baseline, but only two at their final visit. Conclusion: Our findings indicate that TasP is widely accepted among FSWs in Cotonou and could be implemented with relative success. However, due to mobility in this population, follow-up was sub-optimal, suggesting that large geographical coverage of FSW-friendly clinics is needed for sustained treatment implementation. We also fell short of the UNAIDS objective of 90% viral suppression among treated patients, underlining the need for better adherence support programs. [ABSTRACT FROM AUTHOR]

The objective of this paper is to expose those socio-structural contexts revealing the social injustice and human rights violations that sub-Saharan women face every day when forced into sex work by unemployment or sickness. Results of a qualitative study highlighting some key structural determinants of sex work and HIV infection among FSWs will be presented and examined through the lens of the WHO conceptual framework for action on the social determinants of health. The results showed that most FSWs had lacked the necessary financial support at some point in their lives. Also, both the socioeconomic and political context failed to provide proper support to prevent involvement in sex work and the consequent risks of HIV. The cultural and societal values placed on the health and well-being of FSWs in Benin appear to depend on the degree to which sexual violence and adultery are perceived as a collective social concern. This portrait of FSWs calls for both long-term interventions through a structural determinant approach to HIV prevention, targeting all the women who could face such a financial situation well before their entry into sex work, while maintaining short and medium-term interventions on the intermediary determinants. [ABSTRACT FROM AUTHOR]

BLyS/BAFF is recognized for its role in B-cell ontogenesis, as well as cell fate decision towards the first-line/innate marginal zone (MZ) B-cell pool. Excess BLyS/BAFF is associated with hyperglobulinemia and increased frequencies of activated precursor-like MZ B-cells. Herein, we show that HIV highly-exposed seronegative (HESN) commercial sex workers (CSWs) had lower soluble BLyS/BAFF levels and relative frequencies of BLyS/BAFF expressing cells in their genital mucosa when compared to those from HIV-infected CSWs and HIV-uninfected non-CSWs. Furthermore, we identified genital innate and/or marginal zone (MZ)-like CD1c+ B-cells that naturally bind to fully glycosylated gp120, which frequencies were lower in HESNs when compared to HIV-infected CSWs and HIV-uninfected non-CSWs. Although genital levels of total IgA were similar between groups, HESNs had lower levels of total IgG1 and IgG3. Interestingly, HIV-gp41 reactive IgG1 were found in some HESNs. Low genital levels of BLyS/BAFF observed in HESNs may allow for controlled first-line responses, contributing to natural immunity to HIV. [ABSTRACT FROM AUTHOR]

We have previously reported that the female genital tract (FGT) of Beninese HIV highly-exposed seronegative (HESN) commercial sex workers (CSWs), presented elevated frequencies of a myeloid HLA-DR+CD14+CD11c+ population presenting "tolerogenic" monocyte derived dendritic cells (MoDC) features. In order to assess whether a differential profile of monocytes may be involved in the generation of these genital MoDCs, we have herein characterized the blood monocyte compartment of Beninese HESNs (HIV-uninfected ≥ 10 years CSWs) and relevant controls (HIV-uninfected 2.5–5 years CSWs herein termed "early HESNs"), HIV-infected CSWs, and low-risk HIV-uninfected women from the general population. Transcriptomic analyses by RNA-Seq of total sorted blood monocytes demonstrate that in comparison to the control groups, HESNs present increased expression levels of FCGR2C, FCAR, ITGAX, ITGAM, CR2, CD68, and CD163 genes, associated with effector functions. Moreover, we found increased expression levels of genes associated with protection/control against SHIV/HIV such as CCL3, CCL4, CCL5, BHLHE40, and TNFSF13, as well as with immune regulation such as IL-10, Ahr, CD83, and the orphan nuclear receptor (NR)4A1, NR4A2, and NR4A3. Through multicolor flow cytometry analyses, we noticed that the frequencies of intermediate and non-classical monocyte populations tended to be elevated in the blood of HESNs, and exhibited increased expression levels of effector CD16, CD11c, CD11b, as well as regulatory HLA-G, IL-10, and IFN-α markers when compared to HIV-uninfected women and/or HIV-infected CSWs. This profile is compatible with that previously reported in the FGT of HESNs, and likely confers an enormous advantage in their resistance to HIV infection. [ABSTRACT FROM AUTHOR]

• Studies on the incidence and persistence of high-risk human papillomavirus infection among female sex workers (FSWs) in West Africa are scarce. • High incidence and 12-month persistence of HR-HPV infection (38.7%) were found. • Better cervical cancer screening is needed in FSWs. • There is an urgent need for HPV-specific preventive interventions among new FSWs. This study in female sex workers (FSWs) aimed to: (1) estimate type-specific incidence and persistence of human papillomavirus (HPV) infection in Cotonou (Benin) and Bamako (Mali); and (2) identify the factors associated with type-specific incidence and persistence of high-risk HPV (HR-HPV) infection. A 1-year prospective cohort study on cervical cancer screening, and HPV and human immunodeficiency virus (HIV) infections was conducted among FSWs in Cotonou and Bamako from 2017 to 2019. Poisson regression models assessed factors associated with the incidence of HR-HPV infection, while log-binomial regression was performed to identify factors associated with the persistence of HR-HPV infection. Adjusted relative risks (ARR) and 95% confidence intervals (95% CI) were estimated. The incidence of HR-HPV infection was 46.98 per 1000 women-months (predominant types HPV16, HPV35 and HPV59). Factors associated with the incidence of HR-HPV infection were age <20 years (ARR 15.10; 95% CI 3.29–69.19), age at sexual debut <18 years (ARR 6.92; 95% CI 1.97–24.27) and sex work duration ≤1 year (ARR 7.40; 95% CI 1.84–29.69). The persistence of HR-HPV infection at 12 months was 38.7% (most persistent types HPV59, HPV52 and HPV51). Persistence of HR-HPV infection was higher in women with chlamydia (P = 0.031), HIV infection (P < 0.001) and multiple-type HPV infections (P < 0.001). FSWs in West Africa are at high risk of incident and persistent HR-HPV infection, suggesting an urgent need for cervical cancer screening in this population. [ABSTRACT FROM AUTHOR]

Background: Little is known about risk compensation among female sex workers (FSW) on HIV pre-exposure prophylaxis (PrEP), and self-report of sexual behaviors is subject to bias. Setting: Prospective observational PrEP demonstration study conducted among FSW in Cotonou, Benin. Methods: Over a period of 24 months, we assessed and compared trends in unprotected sex as measured by self-report (last 2 or 14 days), by detection of sexually transmitted infections (STIs), and by vaginal detection of prostate-specific antigen and Y-chromosomal DNA, 2 biomarkers of semen exposure in the last 2 or 14 days, respectively. Trends were assessed and compared using a log-binomial regression that was simultaneously fit for all unprotected sex measures. Results: Of 255 participants, 120 (47.1%) completed their follow-up. Prevalence of STI decreased from 15.8% (95% confidence interval: 11.8% to 21.0%) at baseline to 2.1% (95% confidence interval: 0.4% to 10.2%) at 24 months of follow-up (P-trend = 0.04). However, we observed no trend in self-report of unprotected sex in the last 2 (P = 0.42) or 14 days (P = 0.49), nor in prostate-specific antigen (P = 0.53) or Y chromosomal DNA (P = 0.25) over the same period. We observed no statistically significant difference between trends in self-report of unprotected sex and trends in biomarkers of semen exposure in the last 2 days (P = 0.14) or in the last 14 days (P = 0.29). Conclusions: We observed no evidence of risk compensation, and a decrease in STI among FSW on PrEP. PrEP intervention may be an opportunity to control STI among FSW. Future studies should assess risk compensation with biomarkers of semen exposure when possible. [ABSTRACT FROM AUTHOR]

Supplemental Digital Content is Available in the Text. Background: The COVID-19 pandemic indirectly impacts HIV epidemiology in Central/West Africa. We estimated the potential impact of COVID–19-related disruptions to HIV prevention/treatment services and sexual partnerships on HIV incidence and HIV-related deaths among key populations including female sex workers (FSW), their clients, men who have sex with men, and overall. Setting: Yaoundé (Cameroon) and Cotonou (Benin). Methods: We used mathematical models of HIV calibrated to city population–specific and risk population–specific demographic/behavioral/epidemic data. We estimated the relative change in 1-year HIV incidence and HIV-related deaths for various disruption scenarios of HIV prevention/treatment services and decreased casual/commercial partnerships, compared with a scenario without COVID-19. Results: A 50% reduction in condom use in all partnerships over 6 months would increase 1-year HIV incidence by 39%, 42%, 31%, and 23% among men who have sex with men, FSW, clients, and overall in Yaoundé, respectively, and 69%, 49%, and 23% among FSW, clients, and overall, respectively, in Cotonou. Combining a 6-month interruption of ART initiation and 50% reduction in HIV prevention/treatment use would increase HIV incidence by 50% and HIV-related deaths by 20%. This increase in HIV infections would be halved by a simultaneous 50% reduction in casual and commercial partnerships. Conclusions: Reductions in condom use after COVID-19 would increase infections among key populations disproportionately, particularly FSW in Cotonou, who need uninterrupted condom provision. Disruptions in HIV prevention/treatment services have the biggest impacts on HIV infections and deaths overall, only partially mitigated by equal reductions in casual/commercial sexual partnerships. Maintaining ART provision must be prioritized to minimize short-term excess HIV-related deaths. [ABSTRACT FROM AUTHOR]

Background: The COVID-19 pandemic indirectly impacts HIV epidemiology in Central/West Africa. We estimated the potential impact of COVID-19-related disruptions to HIV prevention/treatment services and sexual partnerships on HIV incidence and HIV-related deaths among key populations including female sex workers (FSW), their clients, men who have sex with men, and overall. Setting: Yaoundé (Cameroon) and Cotonou (Benin). Methods: We used mathematical models of HIV calibrated to city population-specific and risk population-specific demographic/behavioral/epidemic data. We estimated the relative change in 1-year HIV incidence and HIV-related deaths for various disruption scenarios of HIV prevention/treatment services and decreased casual/commercial partnerships, compared with a scenario without COVID-19. Results: A 50% reduction in condom use in all partnerships over 6 months would increase 1-year HIV incidence by 39%, 42%, 31%, and 23% among men who have sex with men, FSW, clients, and overall in Yaoundé, respectively, and 69%, 49%, and 23% among FSW, clients, and overall, respectively, in Cotonou. Combining a 6-month interruption of ART initiation and 50% reduction in HIV prevention/treatment use would increase HIV incidence by 50% and HIV-related deaths by 20%. This increase in HIV infections would be halved by a simultaneous 50% reduction in casual and commercial partnerships. Conclusions: Reductions in condom use after COVID-19 would increase infections among key populations disproportionately, particularly FSW in Cotonou, who need uninterrupted condom provision. Disruptions in HIV prevention/treatment services have the biggest impacts on HIV infections and deaths overall, only partially mitigated by equal reductions in casual/commercial sexual partnerships. Maintaining ART provision must be prioritized to minimize short-term excess HIV-related deaths. [ABSTRACT FROM AUTHOR]